Structure-Based Discovery of Natural-Product-like TNF-α Inhibitors

Structure-based discovery of natural-product-like TNF-α inhibitors.

Small but effective: two natural-product-like inhibitors of tumor necrosis factor α (TNF-α; represented in green in the picture) have been identified using structure-based virtual screening. These compounds represent only the third and fourth examples of direct targeting of TNF-α by a small molecule, and display potency comparable to that of the strongest TNF-α inhibitor reported to date.

Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database.

We report herein the identification of an immunomodulatory natural product-like compound as a direct inhibitor of TLR1-TLR2 heterodimerization. Compound suppressed TNF-α and IL-6 secretion in Pam3CSK4-induced macrophages. Moreover, compound inhibited the phagocytic activity of macrophages, presumably through modulation of TLR1-TLR2 signaling and inactivation of NF-κB. Molecular docking revealed...

TNF-α inhibitors: are they carcinogenic?

Biologic therapy has increasingly been used in the treatment of chronic diseases. Tumor necrosis factor (TNF) is a cytokine implicated in the pathogenesis of rheumatoid arthritis and inflammatory bowel disease. Anti-TNF therapy is being used in the treatment of these conditions. Since the introduction of anti-TNF agents, there have been many case reports of development of malignancy after the i...

Mycobacterial Infections Associated with TNF-α Inhibitors

Discovery of novel α-amylase inhibitors using structure-based drug design

a-Amylase is an endoamylase and belongs to glycoside hydrolase family 13 (GH 13) according to the classification of carbohydrate-active enzymes [1]. It initiates starch hydrolysis into smaller oligomers. Inhibitors of this enzyme are of pharmacological importance as a-amylase is considered as attractive target for treating elevated post-prandial blood glucose levels resulting in obesity and typ...